1rsd: Difference between revisions

Line 1:

[[Image:1rsd.gif|left|200px]]<br /><applet load="1rsd" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1rsd.gif|left|200px]]<br /><applet load="1rsd" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1rsd, resolution 2.50Å" />

'''DHNA complex with 3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-[2-(2-hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide'''<br />

==Overview==

Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25), have been discovered using CrystaLEAD X-ray crystallographic, high-throughput screening followed by structure-directed optimization., Screening of a 10 000 compound random library provided several low, affinity leads and their corresponding X-ray crystal structures bound to, the enzyme. The presence of a common structural feature in each of the, leads suggested a strategy for the construction of a directed library of, approximately 1000 compounds that were screened for inhibitory activity in, a traditional enzyme assay. Several lead compounds with IC(50) values of, about 1 microM against DHNA were identified, and crystal structures of, their enzyme-bound complexes were obtained by cocrystallization., Structure-directed optimization of one of the leads thus identified, afforded potent inhibitors with submicromolar IC(50) values.

Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC(50) values of about 1 microM against DHNA were identified, and crystal structures of their enzyme-bound complexes were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC(50) values.

==About this Structure==

1RSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with PSB as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1RSD OCA].

1RSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=PSB:'>PSB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RSD OCA].

==Reference==

Line 14:

[[Category: Single protein]]

[[Category: Staphylococcus aureus]]

[[Category: Betz, S.F.]]

[[Category: Betz, S F.]]

[[Category: Beutel, B.A.]]

[[Category: Beutel, B A.]]

[[Category: Condroski, K.R.]]

[[Category: Condroski, K R.]]

[[Category: Harlan, J.E.]]

[[Category: Harlan, J E.]]

[[Category: Jakob, C.G.]]

[[Category: Jakob, C G.]]

[[Category: Lerner, C.G.]]

[[Category: Lerner, C G.]]

[[Category: Magdalinos, P.]]

[[Category: McCall, J.O.]]

[[Category: McCall, J O.]]

[[Category: Meadows, R.P.]]

[[Category: Meadows, R P.]]

[[Category: Merrick, S.M.]]

[[Category: Merrick, S M.]]

[[Category: Nienaber, V.L.]]

[[Category: Nienaber, V L.]]

[[Category: Sanders, W.J.]]

[[Category: Sanders, W J.]]

[[Category: Severin, J.M.]]

[[Category: Severin, J M.]]

[[Category: Stamper, G.F.]]

[[Category: Stamper, G F.]]

[[Category: Stoll, V.S.]]

[[Category: Stoll, V S.]]

[[Category: Swanson, S.J.]]

[[Category: Swanson, S J.]]

[[Category: Wagner, R.]]

[[Category: Walter, K.A.]]

[[Category: Walter, K A.]]

[[Category: PSB]]

[[Category: 2]]

Line 41:

[[Category: dhna]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 01:50:~~18 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:04 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1rsd.gif|left|200px]]<br /><applet load="1rsd" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1rsd.gif|left|200px]]<br /><applet load="1rsd" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1rsd, resolution 2.50&Aring;" />
 '''DHNA complex with 3-(5-Amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-[2-(2-hydroxymethyl-phenylsulfanyl)-benzyl]-benzamide'''<br />
 ==Overview==
-Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25), have been discovered using CrystaLEAD X-ray crystallographic, high-throughput screening followed by structure-directed optimization., Screening of a 10 000 compound random library provided several low, affinity leads and their corresponding X-ray crystal structures bound to, the enzyme. The presence of a common structural feature in each of the, leads suggested a strategy for the construction of a directed library of, approximately 1000 compounds that were screened for inhibitory activity in, a traditional enzyme assay. Several lead compounds with IC(50) values of, about 1 microM against DHNA were identified, and crystal structures of, their enzyme-bound complexes were obtained by cocrystallization., Structure-directed optimization of one of the leads thus identified, afforded potent inhibitors with submicromolar IC(50) values.
+Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC(50) values of about 1 microM against DHNA were identified, and crystal structures of their enzyme-bound complexes were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC(50) values.
 ==About this Structure==
-RSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with PSB as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RSD OCA].
+RSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=PSB:'>PSB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydroneopterin_aldolase Dihydroneopterin aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.25 4.1.2.25] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RSD OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Staphylococcus aureus]]
-[[Category: Betz, S.F.]]
+[[Category: Betz, S F.]]
-[[Category: Beutel, B.A.]]
+[[Category: Beutel, B A.]]
-[[Category: Condroski, K.R.]]
+[[Category: Condroski, K R.]]
-[[Category: Harlan, J.E.]]
+[[Category: Harlan, J E.]]
-[[Category: Jakob, C.G.]]
+[[Category: Jakob, C G.]]
-[[Category: Lerner, C.G.]]
+[[Category: Lerner, C G.]]
 [[Category: Magdalinos, P.]]
-[[Category: McCall, J.O.]]
+[[Category: McCall, J O.]]
-[[Category: Meadows, R.P.]]
+[[Category: Meadows, R P.]]
-[[Category: Merrick, S.M.]]
+[[Category: Merrick, S M.]]
-[[Category: Nienaber, V.L.]]
+[[Category: Nienaber, V L.]]
-[[Category: Sanders, W.J.]]
+[[Category: Sanders, W J.]]
-[[Category: Severin, J.M.]]
+[[Category: Severin, J M.]]
-[[Category: Stamper, G.F.]]
+[[Category: Stamper, G F.]]
-[[Category: Stoll, V.S.]]
+[[Category: Stoll, V S.]]
-[[Category: Swanson, S.J.]]
+[[Category: Swanson, S J.]]
 [[Category: Wagner, R.]]
-[[Category: Walter, K.A.]]
+[[Category: Walter, K A.]]
 [[Category: PSB]]
 [[Category: 2]]
@@ Line 41: / Line 41: @@
 [[Category: dhna]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 01:50:18 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:04 2008''